Archives of pathology & laboratory medicine最新文献

Context.—: Lymph node (LN) assessment plays a critical role in cancer staging and prognosis but remains a time-consuming and labor-intensive task in pathology. While artificial intelligence (AI) tools have shown promise in improving diagnostic accuracy, their real-world clinical utility in LN metastasis detection across multiple cancer types remains underexplored.

Objective.—: To evaluate the diagnostic performance and efficiency of an AI module in detecting LN metastases from gastric, colorectal, and breast cancers, and to assess its impact on pathologists' workflow.

Design.—: A retrospective study was conducted by using 314 whole slide images from 95 patients who underwent resection for gastric, colorectal, or breast cancer. Three board-certified pathologists reviewed the slides with and without AI assistance. Diagnostic accuracy, review time, and number of mouse clicks required to detect metastases were recorded and compared.

Results.—: AI assistance increased sensitivity-which ranged from 91.8% to 93.9%-to 95.9% for all pathologists, while specificity remained high (97.0%-98.9%). Time to detect LN metastases decreased by up to 78% for some cancer types. The AI-guided click-based review required an average of 1.4 to 5.2 clicks depending on tissue type, with colorectal metastases detected most efficiently. Challenging subtypes, such as breast carcinoma with apocrine differentiation, required more extensive interaction. Micrometastases across all 3 cancer types were successfully identified by the AI.

Conclusions.—: The AI module improved pathologists' sensitivity in detecting LN metastases and significantly reduced review time, particularly for positive nodes. These findings support the integration of AI tools to enhance diagnostic efficiency and accuracy in routine pathology practice.

Context.—: In patients with melanoma, the predictive and prognostic relevance of programmed death ligand 1 (PD-L1) protein expression on tumor cells and tumor-infiltrating lymphocytes (TILs) and of alterations in the gene encoding PD-L1, CD274, are not yet established.

Objective.—: To address these gaps in knowledge.

Design.—: We retrospectively evaluated 64 patients with melanoma treated with immune checkpoint blockade therapy (ICBT) who underwent whole genome sequencing. PD-L1 immunohistochemistry using clone 28-8 was available for 33 of 64 patients. Tumor cell PD-L1 expression was categorized as negative (<1% of cells staining), low (1%-10%), or high (>10%), and TIL PD-L1 expression as low (≤30% of TILs expressing PD-L1) or high (>30%). Event-free survival (EFS) and overall survival were assessed in relation to genetic and histopathologic factors.

Results.—: CD274 alterations were identified in 19% (12 of 64) of tumors and were associated with higher tumor mutational burden. Of 33 tumors assessed by immunohistochemistry, 21 showed PD-L1 positivity in tumor cells, which correlated with higher N category, reduced microsatellite stability, and elevated BRAF (B-Raf proto-oncogene, serine/threonine kinase) alteration rate. High PD-L1 expression on TILs was linked to more advanced disease and increased lymphovascular invasion. Among patients with similar clinical stage, patients receiving PD-L1-targeted ICBT had better EFS and overall survival than patients receiving non-ICBT or excision. Notably, patients with gene amplifications of undetermined significance identified on whole genome sequencing had reduced EFS.

Conclusions.—: Our findings suggest that CD274 alterations, PD-L1 expression on tumor cells and TILs, BRAF mutations, genomic amplifications, and tumor mutational burden may provide meaningful prognostic information in patients with melanoma. Prospective validation in larger cohorts is warranted to confirm the utility of these markers in guiding therapeutic decisions.

Context.—: Promoting diversity, equity, and inclusion (DEI) is crucial for an academic institution's environment and growth. Studies assessing the DEI climate in pathology and laboratory medicine departments are limited and need more data to promote more inclusive workplaces.

Objective.—: To assess the DEI climate and to identify specific, actionable items for improvement in academic pathology and laboratory medicine.

Design.—: A DEI climate assessment survey was prepared with questions related to background demographic information, discriminatory acts, and perceptions of the DEI climate in the workplace and was distributed to 473 people, including faculty, staff, and trainees in the Departments of Anatomic Pathology and Laboratory Medicine at our institution. Data were collected from December 2020 to January 2021.

Results.—: One hundred sixty-four participants responded (35% participation). Up to 48% (76 of 159) reported experiencing some form of discrimination at least once. Gender, age, and race were the most reported bases of discrimination. Females perceived more discrimination (77%; 48 of 62) than male participants (59%; 41 of 69). The top basis of discrimination was race for non-White (14%; 12 of 84) and gender for White (26%; 20 of 78) participants. Trainees were the most common targets and faculty members were the most common source of discrimination. Stress related to reporting was the most common cause that prevented participants from reporting discrimination. Participants reported insufficient DEI mentorship support, discomfort around discussing microaggressions with faculty members, and disbelief in DEI-related contributions being valued for promotion.

Conclusions.—: Performing an anonymous DEI climate survey is an effective way to understand department-specific issues and identify action items for pathology and laboratory medicine departments.

Context.—: Undifferentiated round cell sarcomas (URCSs) are tumors of bone and soft tissue that are heterogeneous in terms of driver events and diverse in their clinical course.

Objective.—: To compare the pediatric BCL6 corepressor (BCOR) and capicua transcriptional repressor (CIC) sarcomas clinically while assessing the utility of advanced diagnostic algorithms.

Design.—: Forty-two histologically diagnosed undifferentiated round cell sarcomas were molecularly characterized using polymerase chain reaction assay, RNA sequencing, and/or NanoString digital bar code technology.

Results.—: The diagnosis of BCOR sarcoma was confirmed in 23 cases, including 17 cases of BCOR::cyclin B3 (CCNB3), 2 cases of BCOR internal tandem duplication, and single cases of BCOR::mastermind like transcriptional coactivator 3 (MAML3) and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein epsilon (YWHAE)::NUT family member 2B (NUTM2B); in 2 cases, the verification was based on gene expression profiles. The primary lesion was localized intraosseously (15 cases; 65%) or originated from soft tissues (8 cases; 35%). Three-year overall survival was 96.0% ± 0.04%. The diagnosis of CIC sarcoma was confirmed in 14 cases, including 5 cases of CIC::double homeobox 4 (DUX4), 4 cases of CIC exon 21 fused to an intergenic region, 2 cases of CIC::double homeobox 4 like 9 (pseudogene) (DUX4L9) and 1 case of CIC::NUTM2B; in 2 cases, verification was based on gene expression profiles. The primary lesion was localized in soft tissues (12 cases; 86%) or intraosseously (2 cases; 14%). Three-year overall survival was 34.4% ± 16.0%.

Conclusions.—: Despite the relatively favorable outcomes in BCOR sarcomas, the relapse rate is considerable, whereas pediatric patients with CIC sarcoma typically develop metastatic disease and have poor outcomes. The data provide a prospective foundation for genetically based therapeutic strategies and risk stratification.

Context.—: Accurate measurement of serum creatinine is essential for estimating glomerular filtration rate (GFR), which is central to chronic kidney disease (CKD) detection, staging, and management. However, historical biases in creatinine measurement among several instrument/assay manufacturers compromised estimated GFR (eGFR) reliability, hindering CKD detection and management. Initiatives led by the National Kidney Disease Education Program (NKDEP) Laboratory Working Group and other stakeholders have standardized calibration of creatinine measurement and reporting of eGFR.

Objective.—: To summarize the journey toward global standardization of serum creatinine measurement procedures, detailing the coordinated efforts that led to calibration traceability to the NIST (National Institute of Standards and Technology) SRM (standard reference material) 967 reference material, examining the role of proficiency testing in monitoring progress, and contrasting the current state of creatinine assay standardization with that of other key kidney function biomarkers, such as cystatin C and urine albumin.

Data sources.—: A comprehensive review of peer-reviewed literature from 2005-2025 was conducted, including landmark studies from the Archives of Pathology & Laboratory Medicine, Clinical Chemistry, and clinical practice guidelines from several professional organizations. College of American Pathologists proficiency testing and LN24 survey data were included.

Conclusions.—: The global creatinine standardization initiative, driven by the NKDEP Laboratory Working Group, has dramatically reduced intermethod bias in serum creatinine measurement procedures, vastly improving the reliability of eGFR. While the metrologic traceability of calibration for creatinine measurement is now harmonized, challenges with analytical specificity, particularly for Jaffe-based methods, remain. The success of creatinine standardization serves as an important model for ongoing efforts to harmonize cystatin C and urine albumin measurements, ultimately leading to more accurate, equitable, and standardized care for patients with or at risk for CKD.

Context.—: Anatomic pathology as a subspecialty has been invaluable in understanding emerging and reemerging infectious diseases throughout many outbreaks and pandemics.

Objective.—: To describe the contributions of the Archives of Pathology & Laboratory Medicine to understanding emerging infections.

Data sources.—: Medical literature and periodicals.

Conclusions.—: The Archives has a long tradition of supporting significant anatomic pathology research into these diseases through timely publishing of original research articles, patient cases, histopathology findings, reviews, and commentaries of public health importance. This was highlighted during the 1976 Legionnaires' disease outbreak in Philadelphia, when the Archives published the first description of the pathologic findings of Legionnaires' disease based on an autopsy study of 26 persons who had died from the novel infection. In that article, John Blackmon, Martin Hicklin, and Francis Chandler at the Centers for Disease Control and Prevention described the pathologic findings of severe pneumonia in all patients and were able to visualize the causative bacillus. The Archives continued to address the importance of emerging infections by publishing a special issue in February 1996 entitled "Emerging and Reemerging Global Microbial Threats." With the increasing importance of emerging infections, a second special issue on this topic was published in August 1997 entitled "Emerging and Reemerging Infectious Diseases." In response to the Zika virus outbreak that began in Brazil in 2015, the Archives became the first peer-reviewed journal to devote a special issue to this emerging viral infection that was causing fetal deaths and congenital malformations, entitled "The Zika Virus Global Pandemic: The Latest Emerging Infection." During the global COVID-19 pandemic, the Archives continued to publish timely articles addressing many important issues about SARS-CoV-2 infections.